ACUTE RENAL FAILURE IN ACUTE KIDNEY INJURY … · ACUTE RENAL FAILURE IN CHILDREN PREVIOUS...
Transcript of ACUTE RENAL FAILURE IN ACUTE KIDNEY INJURY … · ACUTE RENAL FAILURE IN CHILDREN PREVIOUS...
ACUTE RENAL FAILURE IN CHILDREN
PREVIOUS DEFINITION: Sudden (hours,
days) reduction in renal function of at
least 50%, characterized by rising serum
levels of waste products (creatinine,
urea), disturbances in water/electrolyte
balance and urine amount andcomposition.
Irit Krause, M.D.Schneider’s Children Medical Center
ACUTE KIDNEY INJURY NEW DEFINITION
Estimated CCl Urine output
RISK eCCl decrease by 25% <0.5 ml/kg/h for 8 h
INJURY eCCl decrease by 50% <0.5 ml/kg/h for 16 h
FAILURE eCCl decrease by 75% or
eCCl <35 ml/min/1.73 m2
<0.3 ml/kg/h for 24 h or anuric for 12 h
LOSSPersistent failure >4 weeks
END STAGE
End-stage renal disease (persistent failure >3
months)
FROM:
Modified RIFLE criteria in critically ill children with acute kidney injury
A Akcan-Arikan, M Zappitelli, L L Loftis, K K Washburn, L S Jefferson and S L Goldstein (2007)
Causes of acute kidney injury in
children
� Prerenal causes (decreased effective blood volume)
� Altered systemic hemodinamics
� dehydration
� blood loss
� third space losses (burns)
� vasodilatation (septic shock, anaphylaxis, drugs)
� hypoalbuminemia (liver disease, nephrotic syndrome, protein loosing enteropathy)
� heart failure
Causes of AKI - cont
� Altered local hemodinamics
� renal vein thrombosis
� renal artery stenosis/thrombosis
Intrinsic Renal Diseases (1)
� Glomerular (acute glomerulonephritis)
� Vasculitis (Wegener’s, microscopic polyangiitis)
� HUS
� Immune mediated
• Post infectious
• Henoch-Schonlein purpura, IgA nephropathy
• SLE
• Membranoproliferative GN
• anti-GBM associated GN (including Goodpasture)
Intrinsic Renal Diseases (2)
� Tubulointerstitial� Acute tubular necrosis
� Infectious/parainfectious
� Drug related
� Infiltrative (malignancies)
� Exogenous� Drugs (aminoglycosides,
amphothericin, NSAIDs)
� Contrast media
� Rare causes: heavy metals, methoxyflurane, ethylenglycol
� Nehrotoxicity
� Endogenous
� Myoglobin
� Hemoglobin
� Uric acid
� Oxalate
Postrenal Causes
� Obstruction by tumor
� Retroperitoneal fibrosis
� Obstruction by calculi
� Functional obstruction (neurogenic bladder)
� Iatrogenic (following urological operation)
Causes of Renal Failure According to Incidence (Pediatric Nephrology (2002) 17;61-69
Acute Tubular Necrosis
� The most common cause of AKI
Ischemic
Nephrotoxic
Secondary to glomerular disease
Intravascular Volume Depletion
Renal hypoperfusion
Renin↑↑↑↑
Angiotensin↑↑↑↑
Renal vasoconstriction
Endothelin↑↑↑↑
Prostaglandins↑↑↑↑
Systemic
BP
αααα adrenergic
activity↑↑↑↑
↑↑↑↑ ↓↓↓↓
↓↓↓↓
NSAID – kidney enemy!
Pathophysiology of Ischemic Acute Renal Failure
Ischemic Injury
ATP↓↓↓↓ Oxygen mesangial NO endothelin cast
Cytoskeleton radicals contraction formation
Cell swelling
Intracellular Ca↑↑↑↑Activation of phospholipases
proteases
endonucleases
Activation of
leukocytes, thymocytes
Cell damage
cytokines↑↑↑↑Adhesion molecules
Diagnosis
� Acute vs chronic renal failure
� History, previous tests
� Growth
� Kidney size
� Anemia
� Renal osteodystrophy
Prerenal vs. Intrinsic Renal Damage
Fractional excretion of sodium = urinary sodium x serum
creatinine/serum sodium x urinary creatinine x 100% (normal <1%)
� Urine sediment – important!
� Urine electrolytes, including creatinine –important!
� Keep some urine for further tests!
� Ultrasound
� Plain abdomen X-ray
� Specific tests according to the suspected cause (serological investigations)
Treatment (1) - General Principles
� Treating the cause
� Fluid balance including regular weighing
� Evaluation of intravascular volume and effective blood volume (clinical, CVP)
� Avoidance of further renal damage
� hypoxia
� hypovolemia
� nephrotoxic drugs
� contrast material
� Adjustment of drug dosage according to the degree of renal dysfunction
� Nutrition
Hyperkalemia� Glucose 0.5 gm/kg
� Insulin 0.3 units/gm glucose over 2h
� Sodium bicarbonate 1-3mEq/kg and by titration
� Calcium globionate/gluconate (10%) 0.2-0.5mL/kg over 2-5 minutes
� Salbutamol nabulisedintravenous 4-5mcg/kg over 15 min
� Kayexalate (sodium polystyrene sulfonate) 1-2 gr/kg in solution of sorbitol 20% PO or in solution of glucose 10% PR every 4 hours
Treatment (2) – Drug Therapy � Anemia� erythropoietin
� blood transfusions
� Hyperphosphatemia� Phosphor binders (calcium carbonate) with meals
� Hypocalcemia� Ca supplements PO or IV
� Acidosis� sodium bicarbonate (IV continuous- preferable)
Treatments pointed to improve outcome
� Dopamine (“renal dose” 2-5µg/kg/min)
� D1-dopaminergic receptors→ vasodilatation, natriuresis
� No definitive studies showing improved outcome in ARF
� Placebo controlled randomized study of low-dose dopamine in adult critically ill patients with early renal dysfunction did not confer clinically significant protection from renal failure.
� No studies in children
� Adverse effects
� suppression of respiratory drive
� increased cardiac output and myocardial oxygen consumption
� triggering of arrhythmias
� hypokalemia
� High dose dopamine is indicated in cardiac dysfunction
Diuretics- Furoseamide� No studies in children.
� In adults with ARF there is no hard data regarding the benefit of furoseamide.
� Larger doses in children are not more effective. Dosage should not exceed 10mg/kg/day
� Preference to slow infusion
� Adverse effects
� hypokalemia
� hypomagnesemia
� hypercalciuria
� hearing loss
� intravascular volume depletion
� Acts as osmotic diuretic in proximal tubule, increases plasma osmolality and intravascular volume.
� Dose: 0.5-1 gr/kg over 30-60 min.
� Data regarding the effectiveness of mannitol is contradictory.
� In a controlled study of pediatric kidney transplant patients- benefit was shown for mannitol given just prior to clamp removal during the surgery.
Diuretics- Mannitol Natriuretic peptides
� One study showed beneficial effect in ANF.
� Very large multicentral study showed no beneficial effect in patients with oliguric ARF.
� Albumin� No survival benefit in critically ill patients
with ARF.
� Calcium channel antagonists� Have been shown to reduce the incidence
of ATN following renal transplantation
� Clinical use in post-ischemic ARF is not
established.
Future� Fenoldopam mesylate– selective D1-
dopaminergic receptor agonist.
� Melanocyte stimulating factor- anti-inflammatory activity, direct effect on tubules.
� Free radical scavengers.
� IGF-1?
Renal Replacement Therapy
� Absolute indications for dialysis� Fluid overload with pulmonary congestion/heart
failure/uncontrollable hypertension.
� Hyperkalemia
� Acidosis
� Hypocalcemia
� Uremia (encephalopathy, bleeding, pericarditis)
� Intoxications
� Relative indications� Nutritional support impossible d/t fluid restriction
� Very high urea (>300mg%).
� Timing
Choice of Dialysis
� Assessment of patient’s clinical status and specific problems
� Access
� Experience
Peritoneal DialysisIntermittent Hemodialysis
HEMODIAL
FILTRATION
Outcome� Mortality: 35-73% in patients requiring
dialysis
� Prognostic factors
� Cause of ARF
� Presence of multiorgan failure
� Age
� Hypoalbuminemia
� Early dialysis?
� More aggressive dialysis?
Hypertensive Emergencies
� Measurement of blood pressure
� Classification of hypertension by age groups
Malignant Hypertension
Presence of severe hypertension
along with complications:
•papilledema
•neurological
•congestive heart failure
Etiology of Hypertensive Emergencies in Children and Adolescents (1)
� Renal� Acute glomerulonephritis
� Hemolytic uremic syndrome
� Acute renal failure due to other causes
� Acute hydronephrosis
� Chronic renal failure
� Renal artery disease
� Renal vein thrombosis
� Trauma to the kidney
� Post transplantation
� Cardiac
� Coarctation of aorta
� CNS
� Increased intracranial pressure
� Endocrinological
� Pheochromocytoma
� Thyroid storm
� Exogenious agents
� Amphetamins
� Drug withdrawal from anti-hypertensive therapy
� Corticosteroid therapy
Etiology of Hypertensive Emergencies in Children and Adolescents (2)
Treatment Goals
� To treat complications and reduce BP.
� General guidelines: reduce BP by onethird of the difference between thenormal and the elevated values duringfirst 6-8 hours or until resolution ofsymptoms.
Main Drug Groups for
Treatment of Hypertension (1)
� Calcium channel blockers
� Nifedipine (Adalat, Pressolat, Osmoadalat)
� Felodipine (Penedil)
� Amlodipine (Norvasc)
� Nicardipine
� Beta blockers
� Propranolol (Deralin) nonselective
� Atenolol (Normiten) selective
� Central αααα-adrenergic
agonists
� Clonidine (Clonirit)
� Peripheral αααα-blockers
� Prazosin (Hypotense, Minipress)
� αααα and ββββ blockers
� Labetalol
� ACE inhibitors� Captopril (Capoten)
� Enalapril (Convertin)
� Angiotensin II
receptor antagonists� Losartan (Ocsaar)
� Vasodilators� Hydralazine
� Minoxidil
� Sodium nitroprusside
� Diazoxide
� Diuretics
� Loop diuretics
• Furoseamide (Fusid)
� Thiazides
• Hydrochlorothiazide(Disothiazide)
• Metolazone (Zaroxolyn)
� Potassium sparing
• Spironolactone(Aldospirone, Aldactone)
Main Drug Groups for
Treatment of Hypertension (2)
Treatment of Hypertensive Emergencies in Children
Nifedipine 0.25-1mg/kg/dose PO (not sublingual)
Hydralazine 0.15-0.25 mg/kg/dose IV may be repeated every 15 min
Sodium nitroprusside 0.5-1µg/kg/min IV
Captopril 0.1-0.2 mg/kg PO q6h
Diazoxide 1-5mg/kg IV (rapid bolus or continuous infusion)
Labetalol 0.3-1mg/kg/dose IV (may be given by continuous
infusion 0.4-1mg/kg/hr)